American Society of Nephrology Renal Research Report. (65/380)

In the spring of 2004, the Board of Advisors and the Council of the American Society of Nephrology believed it necessary to conduct a series of research retreats to steer priorities appropriately in an era of limited resources. In this regard, retreats were conducted by five working groups in areas that were identified to require distinct attention: acute renal failure, diabetic nephropathy, hypertension, transplantation, and uremic cardiovascular toxicity. The goal of each retreat was to join experts, both within and outside the renal community, to identify areas of basic science and clinical research that should receive highest priority in the next five years. The five retreat summaries with their individual listings of research priorities allow for the distillation of three overriding recommendations that strongly emanate from them: Continued support and expansion of investigator initiated research projects. In each of the five subjects on which this report is focused, there are areas of investigation that require the support of investigator-initiated projects if ultimately progress is to be made in the understanding of the basic mechanisms that underlie the diseases processes on which we want to have an impact in the next decade. It is recommended that there be an expansion of support for research in the areas highlighted in this report that lend themselves to this mechanism of funding by encouraging applications with appropriate program announcements and requests for proposals. In addition to vigorous support for RO1 grants, continued funding of Concept Development and R21/R33 grants is essential to support development of investigator-initiated clinical studies in these areas of high priority. Support for the development of a collaborative research infrastructure. The reader of this article cannot but be impressed by the common theme that independently emerged from each report regarding the urgent need to develop an infrastructure for kidney research. This infrastructure requires the development of core facilities for the centralized processing of biologic materials (genomics, proteomics, and metabolomics), in vivo imaging, development and distribution of antibodies and other molecular reagents, development and distribution and phenotyping of mouse models, and perhaps others. These need to be complemented with core bioinformatics centers that collect and analyze data and finally with a network of clinical study coordinating centers. Expansion of kidney research infrastructure can be achieved by vigorous funding of a program of kidney research core centers. Specifically, we propose that the number of kidney centers be increased with the goal of providing core facilities to support collaborative research on a local, regional, and national level. It should be emphasized that such a program of competitively reviewed kidney core centers would facilitate investigator-initiated research in both laboratory and patient-oriented investigation. This approach is also very much in line with the collaborative research enterprise conceived in the National Institutes of Health's Road Map. Support programs that have an impact on the understanding of the relationship between renal and cardiovascular disease (CVD). It is now widely recognized that chronic kidney dysfunction is an important risk factor for the development of CVD. It therefore is not surprising that essentially every one of the retreat reports emphasizes the urgency to examine this relationship. It is recommended that the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute (NHLBI) work cooperatively to support both basic and clinical science projects that will shed light on the pathogenesis of this relationship and to support the exploration of interventions that can decrease cardiovascular events in patients with chronic kidney disease. Thus, we specifically propose that the NHLBI support investigator-initiated research (RO1, Concept Development, and R21/R33) grants in areas of kidney research with a direct relationship to CVD. Similarly, the NHLBI should work collaboratively with the National Institute of Diabetes and Digestive and Kidney Diseases to support the proposed program of kidney core research centers. This subject provides an excellent opportunity to foment a collaboration between two institutes, along the lines of the present-day overall philosophy of the National Institutes of Health.  (+info)

Nephrologists' experience with and attitudes towards decisions to forego dialysis. The End-Stage Renal Disease Network of New England. (66/380)

Ethicists and lawyers agree that competent adult patients or their surrogate decision-makers have the right to forego life-sustaining treatment, but the views of practicing physicians have not been well-studied. To examine nephrologists' experience with and attitudes towards decisions to forego dialysis, a questionnaire was sent to all 161 nephrologists performing chronic dialysis in six New England states; 118 (73%) responded. The proportion of nephrologists who reported withholding (not starting) dialysis from the cited numbers of patients during the previous year was 11%, 0; 58%, 1 to 5; 20%, 6 to 10; 8%, 11 to 15; and 3%, greater than or equal to 16. For withdrawing (stopping), the proportions were 19%, 0; 73%, 1 to 5; 9%, 6 to 10; and 0%, greater than or equal to 11. The nephrologists withheld dialysis more times than they withdrew it (chi 2 = 26; P = 0.004). If requested to do so by a competent patient, 88% of nephrologists would stop dialysis. If requested by the family of an incompetent patient, 90% would stop if the patient had clear prior wishes, but only 63% would stop if prior wishes were unclear. With competent patients, the issue of withdrawal of dialysis was usually raised by the patient (56%). With incompetent patients, the issue was raised by the family (42%) or nephrologist (30%). It was concluded that decisions to withhold dialysis are more frequent than decisions to withdraw it. Moreover, nephrologists agree about the management of requests to withdraw dialysis in competent patients or incompetent patients with clear prior wishes; they disagree about the management of incompetent patients with unclear prior wishes.(ABSTRACT TRUNCATED AT 250 WORDS)  (+info)

Consequences of inadequate management of hyponatremia. (67/380)

Dilutional hyponatremia is a commonly observed disorder in hospitalized patients. It represents an excess of water in relation to prevailing sodium stores and is most often associated with a high plasma level of arginine vasopressin, including that found in patients with the syndrome of inappropriate antidiuretic hormone secretion. Hyponatremia may be classified as either acute or chronic depending on the rate of decline of serum sodium concentration, and can lead to a wide range of deleterious changes involving almost all body systems. Serious complications of dilutional hyponatremia most frequently involve the central nervous system. In fact, acute severe hyponatremia is potentially life-threatening and must be treated promptly and aggressively. Chronic hyponatremia often develops in patients with nonrenal diseases and is associated with increased morbidity and mortality. In patients hospitalized for congestive heart failure, hyponatremia is linked to a poor prognosis and increased length of hospital stay. Prompt recognition and optimal management of hyponatremia in hospitalized patients may reduce in-hospital mortality and symptom severity, allow for less intensive hospital care, decrease the duration of hospitalization and associated costs, and improve the treatment of underlying comorbid conditions and patients' quality of life. The proper treatment of dilutional hyponatremia, especially when chronic, must avoid increasing serum sodium too rapidly, which can lead to permanent or fatal neurologic sequelae. The treatment of hyponatremia may be facilitated by emerging therapies that block the actions of arginine vasopressin at V2 and V1a receptors to promote aquaresis, the electrolyte-sparing elimination of free water, and elevate serum sodium concentrations.  (+info)

Low rates of testing and diagnostic codes usage in a commercial clinical laboratory: evidence for lack of physician awareness of chronic kidney disease. (68/380)

Improving outcomes for chronic kidney disease (CKD) requires early identification and recognition by physicians. There are few data on rates of testing or use of diagnostic codes for CKD. A cross-sectional analysis was performed of patients who were older than 40 yr and had one or more laboratory tests between April 1, 2002, and March 31, 2003, at a Laboratory Corporation of America regional laboratory. Objectives were to determine the frequency of testing for serum creatinine; prevalence of CKD, defined as estimated GFR <60 ml/min per 1.73 m2; and sensitivity of diagnostic codes for CKD for patients with and without risk factors for CKD and with or without cardiovascular disease (CVD). Of the 277,111 patients, 19% had serum creatinine measured, compared with 33 and 71% who had measurements of serum glucose and lipids, respectively. Patients with hypertension, diabetes, and age >60 yr were more likely to be tested for serum creatinine with odds ratio (OR; 95% confidence interval) of 2.09 (2.05 to 2.14), 1.22 (1.19 to 1.25), and 1.24 (1.22 to 1.27) respectively. Among patients tested, 30% had CKD. Sensitivity and specificity of kidney disease diagnostic codes compared with CKD defined by estimated GFR <60 ml/min per 1.73 m2 were 11 and 96%, respectively. In patients with hypertension, diabetes, age >60 years, and CVD, rates of testing and sensitivity of diagnostic codes were 53 and 14%, respectively. Low rates of testing for serum creatinine and insensitivity of diagnostic codes for CKD, even in high-risk patients, suggests inadequate physician awareness of CKD and limited utility of administrative databases for identification of patients with CKD.  (+info)

Stem cells and cardiovascular and renal disease: today and tomorrow. (69/380)

The traditional view that organs have only limited regenerative capacity has been challenged in recent years as adult bone marrow stem cells as well circulating progenitor cells have been identified to retain the plasticity to participate in neovascularization, a process so far believed not to be possible after birth. An organ that is damaged by ischemia causes the release of cytokines; these act via the flowing blood and stimulate the bone marrow, which then mobilizes progenitor cells to the blood and directs them to adhere to and migrate into the damaged organ. Thus, these progenitor cells most likely constitute a natural repair mechanism that counteracts degenerative or aging processes. On the basis of encouraging experimental data, first clinical trials have been established to demonstrate the safety and the feasibility of progenitor cell therapy in case of peripheral artery disease or myocardial infarction. Trials investigating injection of bone marrow or circulating progenitor cells into the coronary artery after an acute myocardial infarction not only demonstrates safety of the procedure but also gave hints toward efficacy. Nevertheless, these findings have to be validated by subsequent larger, prospective, randomized, controlled trials. There are also potential topics in nephrology, where modification of progenitor cell activity might be of benefit, such as renal ischemic disease, glomerular disease, and renal transplant vasculopathy. Finding a way to integrate the principle of progenitor cell action into therapeutic efforts might provide a completely new therapeutic strategy that not only attempts to retard disease progression but furthermore targets to regenerate damaged organs.  (+info)

Molecular etiology of primary hyperoxaluria type 1: new directions for treatment. (70/380)

Primary hyperoxaluria type 1 (PH1) is a rare autosomal-recessive disorder caused by a deficiency of the liver-specific enzyme alanine:glyoxylate aminotransferase (AGT). AGT deficiency results in increased synthesis and excretion of the metabolic end-product oxalate and deposition of insoluble calcium oxalate in the kidney and urinary tract. Classic treatments for PH1 have tended to address the more distal aspects of the disease process (i.e. the symptoms rather than the causes). However, advances in the understanding of the molecular etiology of PH1 over the past decade have shifted attention towards the more proximal aspects of the disease process (i.e. the causes rather than the symptoms). The determination of the crystal structure of AGT has enabled the effects of some of the most important missense mutations in the AGXT gene to be rationalised in terms of AGT folding, dimerization and stability. This has opened up new possibilities for the design pharmacological agents that might counteract the destabilizing effects of these mutations and which might be of use for the treatment of a potentially life-threatening and difficult-to-treat disease.  (+info)

Analysis of patient flow into dialysis: role of education in choice of dialysis modality. (71/380)

BACKGROUND: Despite advances in predialysis care, morbidity and mortality remain high. OBJECTIVES: To analyze end-stage renal disease (ESRD) patient demographics and clinical data on education on dialysis treatment options, type of chronic renal replacement therapy (RRT), and effects of planned versus non-planned dialysis start. METHODS: 621 patients, from 24 Spanish hospitals, who started RRT in 2002. Peritoneal or vascular access at dialysis initiation was considered "planned." RESULTS: 304 (49%) patients were non-planned and half of them had prior nephrology follow-up. Of the patients with >3 months nephrology follow-up (76% of all), only half were educated on dialysis modalities. Dialysis education was associated with planned start in 73.4% versus 26% in non-educated patients (p < 0.05), shorter follow-up (55 vs 65 months, p = 0.033), more medical visits in the prior year (6.5 vs 4.4, *p < 0.001), more patients starting peritoneal dialysis (31% vs 8.3%*), and more specific follow-up by ESRD unit versus general nephrology care (63% vs 26%*). Non-planned start was associated with older age (63 vs 60.6 years, p = 0.06), fewer medical visits (4.6 vs 6.4*), less education about modality options, and greater use of hemodialysis (92% vs 75%*). Planned patients had better biochemical parameters at start of dialysis. CONCLUSION: Despite nephrology follow-up, half the patients did not have a planned dialysis start. Planned start was associated with better clinical status. More patients chose peritoneal dialysis when educated about dialysis modality options. ESRD-specific units were more likely to provide patient education.  (+info)

Prevention of chronic kidney and vascular disease: toward global health equity--the Bellagio 2004 Declaration. (72/380)

Chronic kidney disease (CKD) not only reflects target organ injury in systemic vascular disease in the general population and in association with diabetes, hypertension, and smoking, but it is recognized as one of the major risk factors in the pathogenesis and outcome of cardiovascular disease. Recent surveys have revealed that the prevalence of CKD, particularly the hidden mild form (mildly elevated levels of serum creatinine or urinary albumin excretion), is surprisingly high in the general population. In recent years, the global epidemic of type 2 diabetes has led to an alarming increase in the number of patients with CKD. Most patients with CKD (over 50 million individuals worldwide) succumb to cardiovascular events, while each year over 1 million develop end-stage renal failure, which requires costly treatment and in many countries of the world, unaffordable renal replacement therapy by chronic dialysis or renal transplantation. Alarmed by the immense challenge to human morbidity and the economic burden of CKD and ensuing systemic cardiovascular disease, the International Society of Nephrology convened a multidisciplinary group of expert physicians and public health leaders from around the world to develop strategies to delay and avert this bleak future by effective prevention of CKD based on awareness, early detection, and effective treatment.  (+info)